Nanoparticles for Effective Delivery of Small Interfering RNA to Reduce Progression of Multiple Myeloma

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Researchers at the University of Pennsylvania, Philadelphia, have made a significant breakthrough in the treatment of multiple myeloma, a type of blood cancer. By using siRNA-based silencing of the protein cyclophilin A (CyPA), they were able to reduce tumor burden and extend the lives of patients.

Published in the journal PNAS, the research paper titled “In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles for multiple myeloma therapy” outlines the development of a targeted nanoparticle platform for delivering nucleic acid therapeutics to bone marrow endothelial cells. This targeted approach shows great promise in the treatment of multiple myeloma.

Multiple myeloma is currently treatable but not curable, with high relapse rates and short survival rates for patients who relapse. The researchers focused on bone marrow endothelial cells, which play a critical role in the progression and resistance to treatment of multiple myeloma. By inhibiting the protein CyPA secreted by these cells, the researchers aimed to slow down the progression of the disease and increase its vulnerability to chemotherapy.

However, delivering inhibiting molecules to the bone marrow endothelium is a challenge. To overcome this hurdle, the researchers turned to a nanoparticle delivery system. They developed nanoparticles composed of a polymer-lipid hybrid material and a lipid-polyethylene glycol (PEG) to encapsulate the nucleic acid therapeutics. These nanoparticles effectively protected the therapeutic payload from degradation and successfully delivered it to the targeted tissues.

In a living mouse model, the researchers demonstrated the efficacy of their nanoparticle delivery platform and the CyPA silencing therapy. The silencing of CyPA reduced multiple myeloma invasion across bone marrow endothelial cells, disrupted interactions, and sensitized cancer cells to the chemotherapy drug bortezomib. This led to reduced proliferation and angiogenesis, ultimately extending the survival of the mice.

The researchers believe that this nanoparticle platform holds great potential for delivering nucleic acid therapeutics to other types of malignancies as well. The study opens up new possibilities for targeted and personalized treatments for various cancers.

More information:
Pedro P. G. Guimarães et al, In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles for multiple myeloma therapy, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2215711120

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Nanoparticles deliver small interfering RNA to slow multiple myeloma (2023, June 17)
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